CN1172746C - Device and method for controlling the quality of microdropletes deposited on a substrate - Google Patents

Device and method for controlling the quality of microdropletes deposited on a substrate Download PDF

Info

Publication number
CN1172746C
CN1172746C CNB00813524XA CN00813524A CN1172746C CN 1172746 C CN1172746 C CN 1172746C CN B00813524X A CNB00813524X A CN B00813524XA CN 00813524 A CN00813524 A CN 00813524A CN 1172746 C CN1172746 C CN 1172746C
Authority
CN
China
Prior art keywords
substrate
light
droplet
image
light source
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Expired - Fee Related
Application number
CNB00813524XA
Other languages
Chinese (zh)
Other versions
CN1377301A (en
Inventor
ʷ�ٷҡ�����˹
史蒂芬·贝克斯
3
霍尔格·格鲁勒
罗兰德·赞格勒
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Hann-Schickard-Gesellschaft fuer Angewandte Forschung eV
Original Assignee
Hann-Schickard-Gesellschaft fuer Angewandte Forschung eV
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Hann-Schickard-Gesellschaft fuer Angewandte Forschung eV filed Critical Hann-Schickard-Gesellschaft fuer Angewandte Forschung eV
Publication of CN1377301A publication Critical patent/CN1377301A/en
Application granted granted Critical
Publication of CN1172746C publication Critical patent/CN1172746C/en
Anticipated expiration legal-status Critical
Expired - Fee Related legal-status Critical Current

Links

Images

Classifications

    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/508Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above
    • B01L3/5085Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above for multiple samples, e.g. microtitration plates
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01JCHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J19/00Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J19/0046Sequential or parallel reactions, e.g. for the synthesis of polypeptides or polynucleotides; Apparatus and devices for combinatorial chemistry or for making molecular arrays
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/17Systems in which incident light is modified in accordance with the properties of the material investigated
    • G01N21/25Colour; Spectral properties, i.e. comparison of effect of material on the light at two or more different wavelengths or wavelength bands
    • G01N21/251Colorimeters; Construction thereof
    • G01N21/253Colorimeters; Construction thereof for batch operation, i.e. multisample apparatus
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01JCHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00583Features relative to the processes being carried out
    • B01J2219/00603Making arrays on substantially continuous surfaces
    • B01J2219/00646Making arrays on substantially continuous surfaces the compounds being bound to beads immobilised on the solid supports
    • B01J2219/0065Making arrays on substantially continuous surfaces the compounds being bound to beads immobilised on the solid supports by the use of liquid beads
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01JCHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00583Features relative to the processes being carried out
    • B01J2219/00603Making arrays on substantially continuous surfaces
    • B01J2219/00659Two-dimensional arrays
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01JCHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/0068Means for controlling the apparatus of the process
    • B01J2219/00693Means for quality control

Abstract

A device for controlling the quality of microdroplets deposited on a substrate comprises a light source for illuminating the substrate which has the microdroplets deposited thereon. An image generator is provided for receiving the light which has been produced by the light source, fallen through the substrate or reflected by the substrate, so as to generate an image. Furthermore, an identifier and an analyzer are provided for analyzing the generated image with respect to patterns created in said image as a result of a refractive effect produced by microdroplets deposited on the substrate.

Description

Be used to control the apparatus and method that are deposited on the quality of microdropletes on the substrate
The present invention relates to a kind of apparatus and method that are deposited on the quality of microdropletes on the substrate that are used to control, particularly a kind of apparatus and method of when making so-called microarray, quality being controlled of being suitable for.Title microarray representative is in droplet regularly arranged of liquid state or drying regime on substrate.This is arranged in its substrate that promptly has printing microarray thereon on the whole, is commonly called biochip.Be made up of carrier solution under the droplet normal condition, substance dissolves is in carrier solution.The single droplet of microarray generally be dissolved in drop in material different.
Impose in the situation of carrier substrate at multiple known substance, this biochip can be regarded as the analytical instrument of highly-parallel in essence; Known substance can be with particular form and another kind of regulation substance reaction.When unknown sample contacts with biochip, each of a plurality of points of microarray will be reacted with sample liquids on the biochip.By analyzing the reaction pattern on this biochip, can draw the relevant material that is included in the unknown sample.Thereby the kind that is deposited on the multiple material on the biochip is directly relevant with the quantity of the analysis that can promptly pass through this biochip executed in parallel simultaneously.
Consider that these biochips are used as analysis and diagnostic instrments, obviously continuous quality control is most important when making these biochips.
In order to apply multiple material to supporting substrate, in the situation of each point of making microarray with dispersing mixer, must use three kinds of different technology, promptly online synthetic, contact print or so-called " fixed point ".When coated droplet, their desiccation, substance dissolves are on substrate surface in the remaining liquid.When material is put into humid air, make moisture condense in the position of deposited material, can rebuild the initial configuration of droplet.
For the control of implementation quality in the manufacture process of these biochips, must find out after applying droplet, whether these droplets have been made into microarray, and if be made into microarray, where they are created in.
For example, knownly coming from above with the CCD gamma camera in the situation of droplet image on the recording carrying body, discerning implementation quality control, estimating then by automated graphics.This image can be used for determining the existence of each single droplet of microarray and definite local location.But, the functional reliability of this Flame Image Process depends on that consumingly droplet is different from the contrast of background on every side.In addition, usually from droplet, distinguish out pollutant such as grit has suitable difficulty, perhaps can not distinguish grit and droplet at all, perhaps the grit adjunct drop that disguises oneself as.Following owing to carry out quality control unsatisfactorily, this traditional image processing apparatus often causes the mistake in the process control.
US-5,508,200 have disclosed a kind of chemico-analytic method and apparatus that is used to carry out.For this purpose, at first cause the chemical reaction between the differential responses position at the diverse location place of the surveyed area of sample carrier.Then, record is also handled the complete digital picture of surveyed area, so that obtain the detection by quantitative result for the example reaction at the diverse location place of surveyed area, the function of optical change takes place as diverse location place in surveyed area.
The object of the present invention is to provide a kind ofly to be used to control the economically valuable of the quality that is deposited on the droplet on the substrate and the device of reliable in function, and the method for a kind of economically valuable and reliable in function.
According to the present invention, a kind of device that is deposited on the transparent quality of microdropletes on the substrate that is used to control is provided, comprising:
One light source, being used for throwing light on parallel rays deposits the substrate of transparent droplet on it;
One image forming appts is used to receive the light that is produced and passed through substrate or reflected by substrate by light source, so that produce image;
Be used at described image for the device of discerning by the pattern that refraction effect produced of the nonreentrant surface generation that is deposited on the transparent droplet on the substrate; And
Be used for the device of existence, position and/or the image that dimension analysis produced of the transparent droplet that on being identified on the basis of pattern, deposits, pick out transparent droplet from solid particle by described pattern with respect to substrate.
According to the present invention, a kind of method for quality that is deposited on the transparent droplet on the substrate that is used to control is provided, may further comprise the steps:
A) utilize light source to throw light on and deposit the substrate of transparent droplet on it with parallel rays;
B) receive the light that produces and pass through substrate or reflect by this light source, so that produce image by substrate;
C) discern for the pattern that refraction effect produced that in described image, produces by the nonreentrant surface that is deposited on the transparent droplet on the substrate; And
D) this image of existence, position and/or dimension analysis of the transparent droplet that deposits on being identified on the basis of pattern with respect to substrate picks out transparent droplet by described pattern from solid particle.
The present invention makes on the basis that discovery can expertly utilize the refraction of liquid curved surface glazing that the quality that is applied to the droplet on transparent or transparent substrates or the reflection substrate is controlled.Owing to the refraction that utilizes light has improved the contrast of institute's document image, thereby can in image, identify droplet with very dark spot pattern form record.
About this point, when utilizing, do not consider the minute differences in the material multiple combination situations, droplet has nonreentrant surface usually, and this convex surface has the anaclasis characteristic similar to convex lens.Can utilize the strong light refraction of the light that on drop, produces by this convex lens in the mode that middle finger above goes out, produce the high-contrast image of this droplet.
In other words, the present invention has utilized the big more effect of curvature of the more little droplet surface of diameter of droplet.Illustrated as mentioned like that, the droplet that these can be had curved surface is regarded lenticule as because the different refractive index of boundary between drop and the surrounding air, light is diffracted.Curvature is big more, and promptly drop is more little, and these lenticular focal lengths will be short more.
When using, compare the focal length that to ignore droplet with the distance of image forming appts according to apparatus and method of the present invention.Thereby, will be distributed on the whole upper half-space from light below by drop.Distance between image forming appts and the drop is for example so big, makes this image forming appts only survey the very little part of this semispace, promptly has the part of little solid angle.When image forming appts is watched, this means with the surrounding environment of droplet and compare that it is darker that droplet seems.
When use transparency carrier as carrier when for example depositing the biochip of microarray on it, can obtain high-contrast image.This transparency carrier that deposits microarray on it is introduced in the light source and the light path between the image forming appts that extends in uniform space, make image forming appts to see a white background, and exist the position light of droplet diffracted at other in the position that does not deposit little drop.This will cause high-contrast image, wherein droplet can be identified as the faint spots pattern.
Perhaps, light source and image forming appts can be arranged on the same side mutually of reflection substrate, make image forming appts receive the light that substrate reflected.
In addition, by utilizing droplet in image forming appts, to form the picture of entire circumference environment, make droplet also will form this fact of picture of light source, might be from solid particle, for example identify droplet in the grit, in other things, light source is visible as the small light spot of the center of the droplet that shows as dim spot in image.Grit with regulation center pit is unlikely to produce this little speck.Thereby on the basis of above-mentioned effect, definitely can from solid, identify liquid object.
Advantageously, by the picture that utilizes the automatic analysis image generation device of image processing apparatus to be produced, device according to the present invention and the method according to this invention can be used as line Quality Control, wherein when adopting according to mechanism of the present invention, image processing apparatus can the advantageously existence of identification droplet on the basis of the specific pattern that above-mentioned droplet produced.Therefore, the present invention may prepare a kind of system that is used to control the quality that is deposited on the droplet on the substrate, and this system is moderate on price on the one hand, and this systemic-function is reliable on the other hand.This substrate can be transparent, reflection or partially transparent, or partial reflection.The present invention can be advantageously used in the quality in the control biochip manufacture process especially.
In claims, enumerate the present invention and further improved structure.
Explain most preferred embodiment of the present invention below with reference to accompanying drawings in detail, wherein:
Fig. 1 is a schematic cross sectional view, is used to the result of use of explaining that the present invention produces;
Fig. 2 schematically shows an embodiment of the apparatus according to the invention;
Fig. 3 schematically shows the image that deposits the transparency carrier of droplet on its that is produced; And
Fig. 4 schematically shows the further improvement structure according to the embodiment of apparatus of the present invention.
Referring to Fig. 1, at first will explain the result of use that the present invention produces.For this purpose, in Fig. 1, express transparency carrier 2, the surface of this substrate 2 has deposition droplet 4 thereon.Droplet 4 can be, the droplet of the microarray of biological example chip, thereby this transparency carrier 2 is the carrier substrate of biochip.The light that light source produced that extends by uniform space in Reference numeral 6 presentation graphs 1.Be known in the art and produce this parallel rays 6 by uniform source of light.
As can be seen from Figure 1, the droplet 4 on substrate 2 is that drop has nonreentrant surface 4 '.About this point, will be with reference to such fact, promptly the true form of drop 4 depends on the surface tension of liquid and the character of surface of baseplate material on substrate 2.But, do not consider the minute differences that exists in the material multiple combination situations always to have nonreentrant surface 4 '.
With regard to the refraction of light, this nonreentrant surface 4 ' has the characteristic similar to those convex lens, and is represented as focus among Fig. 18.Droplet is more little on substrate, and then the curvature on surface 4 ' is big more, thereby refraction effect is strong more.Because this refraction effect except non-diffraction light 6 ', also can obtain the refracted ray 6 that is produced by curved surface 4 ' ".
Can utilize this high light of the drop place light that the front described in detail with reference to Fig. 1 to learn refraction now, produce the high-contrast image of droplet.
Represent in order to realize an embodiment of the required device of this purpose by the example among Fig. 2.This device comprises that one produces the light source 10 of parallel beam 6, and the transparency carrier 2 that deposits droplet 4 on it inserts in the light path of these parallel rayss 6.Light source 10 produces the illumination that extend in uniform space.
The light source that extend in this uniform space can be any known luminaire that can produce parallel rays 6.In addition, light source 10 can comprise any optical devices that are used to produce this light.
In Fig. 2, also express the focus 8 of the convex surface 4 ' of the droplet 4 that can produce refraction effect.In addition, in Fig. 2, express refracted ray 6 once more " and diffracted ray 6 ' not.
The side relative that photo-detector 12 is arranged on transparency carrier 2 with light source 10; This photo-detector 12 is surveyed by light source 10 emissions and the light by transparency carrier 2, and promptly refracted ray 6 ", and the light 6 ' of diffraction not.Photo-detector 12 can be traditional gamma camera, for example the CCD gamma camera.
Shown in the structure, wherein light source 10, substrate 2 and gamma camera 12 are arranged on one " line ", optical detector 12 produces very bright for the position that does not deposit drop 4 on substrate 2 or white image is regional.Gamma camera 12 is seen a white background.Exist droplet for example to have the position of droplet 4 at other, as has been describ, light is refracted, and droplet produces and is equivalent to lenticular effect, forms the picture of whole background in gamma camera.Owing to compare with the light that light source is produced, surrounding environment brightness is darker, so droplet 4 shows as very dark zone 14 on the picture that gamma camera 12 is produced, as from schematically showing as can be seen Fig. 2.
Droplet has formed the image of entire environment in gamma camera, thereby has also formed the image of light source, and the image of light source shows as a sparklet in the center of the dark areas that droplet produced.Thereby droplet 4 is created in the picture of schematically being expressed by mark 14 and 16 among Fig. 2.In addition, in photo-detector 12, schematically show this picture by dark areas 18.
Thereby the device shown in Fig. 2 provides high-contrast image, wherein presents very dark droplet before very bright background.
Express the picture 20 of the droplet that is produced by this device in Fig. 3, wherein microarray comprises 4 * 6 droplets, i.e. 24 droplets, and mark 4 is only expressed one of them droplet in Fig. 3.As can be seen from Figure 3, each in these droplets produces a dim spot 14 in this image; In the center of this dim spot 14, can see one by sparklet 16 that light source image produced.Utilize this bright spot, in that in this way produce and image as shown in Figure 3, can very well from drop, identify grit.In the device of type shown in Figure 2, grit heart place generation does not therein have the blackening of sparklet.This spot is expressed as 22 in Fig. 3.Under the help of appropriate image processing device, can be at an easy rate from the center has the spot of bright spot, identify spot 22, thereby may from grit, automatically identify droplet.
Be noted that herein the grit with regulation center pit unlikely produces the similar bright spot of bright spot that is produced with droplet, thereby on the basis of above-mentioned effect, must never produce the liquid object that identifies the generation refraction effect in the solid of refraction effect.
To consider such fact, and because direct backlight in the device shown in Figure 2,, make and can not detect grit when image handled, therefore needn't filter so quite little grit will be flooded fully.But, can be with the suitable filtering mechanism spot 22 that filtering is produced by big grit in mode noted earlier from image.
In case carried out record, existence, position and/or the size of droplet in the image shown in can analysis chart 3.
Different with legacy system, described device is extremely insensitive to parasitic light or the indoor general brightness studied, owing to compare the indoor general brightness that can ignore the brightness of parasitic light or be studied with background luminance.This is because as from can being clear that Fig. 2, gamma camera be we can say and directly seen this fact of light source.
Expression is according to another embodiment of apparatus of the present invention among Fig. 4.In the situation of this embodiment, light source 10 and image forming appts 12 are arranged on the same side mutually of the substrate 2 ' of reflection or partial reflection at least.The light 6 that is produced by light source 10 is not reflected in the image forming appts 12 by substrate 2 ' intrusively, unless light 6 is by droplet, as light 6 ' schematically shows.But, if light 6 is incident on the drop 4, these drops will produce once more and be equivalent to the effect that lens produce, with distribution of light in big solid angle, as by 6 " schematically the expression.Most of light in these light will can not hit image forming appts 12.Thereby, for image forming appts 12, to compare with the substrate regions that does not have drop, it is still very dark that drop 4 seems once more.
By using additional lens, can further be optimized said apparatus according to the present invention, use these lens to make in gamma camera the best possible picture that forms expansion light source.Also may between transparency carrier 2 and light source 10, perhaps between transparency carrier 2 and photo-detector 12, catoptron be set, make that neatly each element being carried out the space is provided with.
Thereby the invention provides the quality control to depositing droplets on the substrate of a kind of economically valuable and reliable in function, the present invention is particularly useful for controlling the manufacturing of microarray.The present invention is particularly suitable for line Quality Control, and reliability of the present invention can make the error in the processing controls minimize.

Claims (11)

1. one kind is used for control and is deposited on substrate (2; The device of transparent droplet (4) quality 2 ') comprises:
One light source (10), being used for throwing light on parallel rays deposits the substrate (2,2 ') of transparent droplet (4) on it;
One image forming appts (12) is used for receiving the light that is produced and passed through substrate (2) or reflected by substrate (2 ') by light source (10), so that produce image (20);
Be used at described image (20) for the device of discerning by the pattern that refraction effect produced (14,16) of the nonreentrant surface generation that is deposited on the transparent droplet (4) on the substrate (2,2 '); And
Be used for being identified on the basis of pattern with respect to substrate (2; 2 ') go up existence, the position of the transparent droplet (4) that deposits and/or the device of the image (20) that dimension analysis produced, pick out transparent droplet (4) from solid particle (22) by described pattern (14,16).
2. device according to claim 1, wherein said substrate (2) is a transparency carrier, described light source is set at a side of described substrate, described image forming appts is arranged on the opposite side of described substrate, and described image forming appts (12) is configured to make it to be suitable for receiving light by described substrate.
3. device according to claim 2, wherein this light source (10) and image forming appts (12) are positioned opposite to each other, and transparency carrier (2) is suitable for being arranged on therebetween.
4. device according to claim 1, wherein this substrate (2 ') is a reflection substrate, and this image forming appts (12) is configured to make it to be suitable for receiving the light that described substrate reflects.
5. according to described device one of in the claim 1 to 4, wherein this light source produces the illumination that extend in uniform space.
6. device according to claim 4 also comprises a lens devices in addition, is used for forming at image forming appts (12) optimized image of the light source (10) that extends in this space.
7. device according to claim 4 also comprises catoptron in addition.
8. one kind is used for control and is deposited on substrate (2; The method for quality of the transparent droplet (4) 2 ') may further comprise the steps:
A) utilize light source (10) to throw light on and deposit the substrate (2 of transparent droplet (4) on it with parallel rays; 2 ');
B) receive the light that produces and pass through substrate (2) or reflect by this light source (10), so that produce image (20) by substrate (2 ');
C) discern for the pattern that refraction effect produced (14,16) that in described image (20), produces by the nonreentrant surface that is deposited on the transparent droplet on the substrate (2,2 '); And
D) this image of existence, position and/or dimension analysis (20) of the transparent droplet (4) that deposits on being identified on the basis of pattern with respect to substrate picks out transparent droplet (4) by described pattern (14,16) from solid particle (22).
9. method according to claim 8, wherein this substrate (2) is a transparency carrier, and receives the light by described substrate (2) in step b).
10. method according to claim 8, wherein this substrate (2 ') is a reflection substrate, and receives in step b) by the light of described substrate (2 ') reflection.
11. described method one of in 10 according to Claim 8 is wherein by forming transparent droplet (4) with substance dissolves in carrier solution.
CNB00813524XA 1999-10-05 2000-10-05 Device and method for controlling the quality of microdropletes deposited on a substrate Expired - Fee Related CN1172746C (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE19947878A DE19947878C1 (en) 1999-10-05 1999-10-05 Apparatus useful for empirical quality control of microdroplets on transparent substrate, especially microarrays on biochips, comprises focuses and analyses droplet image patterns
DE19947878.3 1999-10-05

Publications (2)

Publication Number Publication Date
CN1377301A CN1377301A (en) 2002-10-30
CN1172746C true CN1172746C (en) 2004-10-27

Family

ID=7924520

Family Applications (1)

Application Number Title Priority Date Filing Date
CNB00813524XA Expired - Fee Related CN1172746C (en) 1999-10-05 2000-10-05 Device and method for controlling the quality of microdropletes deposited on a substrate

Country Status (10)

Country Link
US (1) US20020176072A1 (en)
EP (1) EP1218106B1 (en)
JP (1) JP2003511653A (en)
CN (1) CN1172746C (en)
AT (1) ATE235315T1 (en)
AU (1) AU771198B2 (en)
CA (1) CA2385536A1 (en)
DE (2) DE19947878C1 (en)
HK (1) HK1047410B (en)
WO (1) WO2001024932A1 (en)

Families Citing this family (18)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2002064255A1 (en) * 2001-02-15 2002-08-22 Scientific Generics Limited Biochip array
JP4545974B2 (en) * 2001-03-26 2010-09-15 キヤノン株式会社 Method and apparatus for manufacturing probe carrier
DE10232409A1 (en) * 2002-07-17 2004-02-05 Picorapid Technologie Gmbh Determining position of substance on microscope slide, employs optical sensor on other side of slide
US6700656B1 (en) * 2002-09-17 2004-03-02 The United States Of America As Represented By The Administrator Of National Aeronautics And Space Administration Flow visualization and characterization of evaporating liquid drops
EP2392402A3 (en) 2004-02-18 2012-03-21 Life Technologies Corporation Multi-step bioassays on modular microfluidic application platforms
TWI356036B (en) * 2004-06-09 2012-01-11 Smithkline Beecham Corp Apparatus and method for pharmaceutical production
DE502004005365D1 (en) * 2004-09-10 2007-12-13 Cognis Ip Man Gmbh Method for the quantitative measurement of deposition on solid surfaces
US20090038407A1 (en) * 2005-03-14 2009-02-12 Federalnoe Gosudarstvennoe Unitarnoe Predprijatie Central Aerohydrodynamic Institute Method of gas or liquid flow visualization on an object surface
US9488597B2 (en) * 2011-11-30 2016-11-08 Corning Incorporated Apparatus and methods for determining surface compliance for a glass surface
JP6111425B2 (en) * 2013-07-05 2017-04-12 株式会社Joled Board inspection method
JP2015065299A (en) * 2013-09-25 2015-04-09 富士フイルム株式会社 Pattern quality management chart, pattern quality management method and pattern formation method
JP5982341B2 (en) * 2013-09-25 2016-08-31 富士フイルム株式会社 Pattern quality control chart, pattern quality control method, and pattern formation method
DE102013111780B4 (en) * 2013-10-25 2016-02-04 Technische Universität München Method and device for determining a property of an object
GB201518392D0 (en) * 2015-10-16 2015-12-02 Isis Innovation Microfluidic arrangements
US11590503B2 (en) 2015-10-16 2023-02-28 Oxford University Innovation Limited Microfluidic arrangements
GB201614150D0 (en) 2016-08-18 2016-10-05 Univ Oxford Innovation Ltd Microfluidic arrangements
FR3067043B1 (en) * 2017-06-02 2021-06-25 Univ De Lille 1 Sciences Et Technologies OPTICAL DETECTION PROCESS
CN108786942B (en) * 2018-06-15 2020-12-18 京东方科技集团股份有限公司 Microfluidic chip, microfluidic device and control method thereof

Family Cites Families (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4959301A (en) * 1988-04-22 1990-09-25 Massachusetts Institute Of Technology Process for rapidly enumerating viable entities
US5508200A (en) * 1992-10-19 1996-04-16 Tiffany; Thomas Method and apparatus for conducting multiple chemical assays
US5373964A (en) * 1993-06-23 1994-12-20 Moore; Sidney D. Eyedrop dispenser with focusing liquid lens
DE4404276C1 (en) * 1994-02-10 1995-03-30 D & R Ferstl Gmbh Method and device for measuring the interfacial surface tension from the drop profile of a sample
US6015880A (en) * 1994-03-16 2000-01-18 California Institute Of Technology Method and substrate for performing multiple sequential reactions on a matrix
US5607565A (en) * 1995-03-27 1997-03-04 Coulter Corporation Apparatus for measuring analytes in a fluid sample
US5585639A (en) * 1995-07-27 1996-12-17 Hewlett-Packard Company Optical scanning apparatus
JPH09189533A (en) * 1996-01-11 1997-07-22 Tokai Rika Co Ltd Deposit sensor and deposit-sensitive wiper
US6020704A (en) * 1997-12-02 2000-02-01 Valeo Electrical Systems, Inc. Windscreen sensing and wiper control system
US6207967B1 (en) * 1999-03-04 2001-03-27 Valeo Electrical Systems, Inc. Off the glass imaging rain sensor
US6347857B1 (en) * 1999-09-23 2002-02-19 Encad, Inc. Ink droplet analysis apparatus
US6232072B1 (en) * 1999-10-15 2001-05-15 Agilent Technologies, Inc. Biopolymer array inspection

Also Published As

Publication number Publication date
EP1218106A1 (en) 2002-07-03
ATE235315T1 (en) 2003-04-15
US20020176072A1 (en) 2002-11-28
HK1047410A1 (en) 2003-02-21
JP2003511653A (en) 2003-03-25
WO2001024932A1 (en) 2001-04-12
CA2385536A1 (en) 2001-04-12
AU771198B2 (en) 2004-03-18
AU1133601A (en) 2001-05-10
HK1047410B (en) 2005-04-01
EP1218106B1 (en) 2003-03-26
DE50001581D1 (en) 2003-04-30
DE19947878C1 (en) 2001-04-05
CN1377301A (en) 2002-10-30

Similar Documents

Publication Publication Date Title
CN1172746C (en) Device and method for controlling the quality of microdropletes deposited on a substrate
CN101813617B (en) Microarray having bright fiducial mark and method of obtaining light data from the same
EP1239279B1 (en) Biochip reader
US5827748A (en) Chemical sensor using two-dimensional lens array
CA2232223C (en) Readhead for a photometric diagnostic instrument
US20100151474A1 (en) Multifunctional Device For Diagnostics and Method For Testing Biological Objects
EP1983331A3 (en) Biochip reader and system for reading image data according to samples on a biochip
US20020016011A1 (en) Analytical apparatus
US5466927A (en) Inspection of translucent containers
WO2001034846A2 (en) Direct mapping of dna chips to detector arrays
US6861251B2 (en) Translucent solid matrix assay device for microarray analysis
CN1388890A (en) Transparent liquid testing apparatus, transparent liquid testing method, and transparent liquid coating method
CN1697974A (en) Methods to view and analyze the results from diffraction-based diagnostics
JP2007263974A (en) Analyte assay using particulate label
CN101799422A (en) Microarray reaches the method that obtains the light data from microarray with substrate, microarray method for making
US7705976B2 (en) Method for recognizing patterns from assay results
CN1220872C (en) Method and device for recording images of grains from cereals to detect cracking
US20070099240A1 (en) Pixel arrays
US5436722A (en) Device for optimally illuminate bottles for bottom inspection
US20030155528A1 (en) Method and apparatus for immediately determining microorganism
CA2158340A1 (en) Enhanced microtitre plate and immunoassays conducted therein
CN1618257A (en) Test method
KR102155218B1 (en) Method of analysing biomaterial
US20200011862A1 (en) Apparatus and method for antibody detection
US20020182111A1 (en) Method and apparatus for visible spectrum imaging

Legal Events

Date Code Title Description
C10 Entry into substantive examination
SE01 Entry into force of request for substantive examination
C06 Publication
PB01 Publication
C10 Entry into substantive examination
SE01 Entry into force of request for substantive examination
C14 Grant of patent or utility model
GR01 Patent grant
REG Reference to a national code

Ref country code: HK

Ref legal event code: GR

Ref document number: 1047410

Country of ref document: HK

C19 Lapse of patent right due to non-payment of the annual fee
CF01 Termination of patent right due to non-payment of annual fee